Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology

Chronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen in ageing, and are likely to be mediated by sustained alterations in gene expression, which may be caused by epigenetic changes such as tissue-specific DNA methylation. We aimed to investigate tissue specific changes in DNA methylation that occur in CKD-related CVD. Genome-wide DNA methylation changes were examined in bisulphite converted genomic DNA isolated from the vascular media of CKD and healthy arteries. Methylation-specific PCR was used to validate the array data, and the association between DNA methylation and gene and protein expression was examined. The DNA methylation age was compared to the chronological age in both cases and controls. Three hundred and nineteen differentially methylated regions (DMR) were identified spread across the genome. Pathway analysis revealed that DMRs associated with genes were involved in embryonic and vascular development, and signalling pathways such as TGFβ and FGF. Expression of top differentially methylated gene HOXA5 showed a significant negative correlation with DNA methylation. Interestingly, DNA methylation age and chronological age were highly correlated, but there was no evidence of accelerated age-related DNA methylation in the arteries of CKD patients. In conclusion, we demonstrated that differential DNA methylation in the arterial tissue of CKD patients represents a potential mediator of arterial pathology and may be used to uncover novel pathways in the genesis of CKD-associated complications

Crafting a Network Plan for a Microfinancing Establishment and Its Branch Network through Virtual Private Network (VPN) Implementation

This study successfully designed a network plan incorporating a Virtual Private Network (VPN) for Kasipag Microfinancing Incorporated (KMI). Employing a developmental research design approach and following the network development life cycle stages of planning, analysis, design, and simulation, the researchers evaluated the feasibility of the network design for implementation in KMI. The findings strongly recommend KMI to proceed with the implementation of the designed network plan that includes a VPN, as it offers significant benefits and advantages. Implementing a VPN in KMI's network infrastructure will greatly enhance network security and enable secure remote access to valuable resources, which is particularly crucial in today's digital landscape emphasizing remote work and data privacy. The thorough simulation of the network plan confirms its feasibility and ensures KMI will have a reliable and efficient network infrastructure. Additionally, the implementation of the network plan will provide KMI with a competitive edge by enabling seamless communication and streamlined data transfer between branches. This will enhance collaboration, improve operational efficiency, and increase overall organizational effectiveness. The cost analysis conducted by the researchers guarantees that the project remains within budget, offering KMI a clear breakdown of expenses for informed decision-making. In conclusion, the recommended implementation of the network plan incorporating a VPN will empower KMI with improved network security, secure remote access, and a competitive advantage in the microfinancing industry. By embracing these advancements, KMI can foster growth, productivity, and success in the ever-evolving digital landscape

Why do people fail to turn good intentions into action? : The role of executive control processes in the translation of healthy eating intentions into action in young Scottish adults

Non peer reviewedPublisher PD

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

Local antiferromagnetic exchange and collaborative Fermi surface as key ingredients of high temperature superconductors

Cuprates, ferropnictides and ferrochalcogenides are three classes of unconventional high-temperature superconductors, who share similar phase diagrams in which superconductivity develops after a magnetic order is suppressed, suggesting a strong interplay between superconductivity and magnetism, although the exact picture of this interplay remains elusive. Here we show that there is a direct bridge connecting antiferromagnetic exchange interactions determined in the parent compounds of these materials to the superconducting gap functions observed in the corresponding superconducting materials. High superconducting transition temperature is achieved when the Fermi surface topology matches the form factor of the pairing symmetry favored by local magnetic exchange interactions. Our result offers a principle guide to search for new high temperature superconductors.Comment: 12 pages, 5 figures, 1 table, 1 supplementary materia

KIR-HLA interactions extend human CD8+ T cell lifespan in vivo

BACKGROUND. There is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell–mediated control of chronic viral infection and that these results are consistent with an increase in the CD8+ T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo. METHODS. We used stable isotope labeling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections. RESULTS. We showed that an individual’s iKIR-ligand genotype was a significant determinant of CD8+ T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory CD8+ T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory CD8+ T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the CD8+ and CD4+ T cell immune aging phenotype. CONCLUSIONS. Together, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival

An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two `relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report the discovery of a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decline of its light curve follows the predicted mass accretion rate, and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about 2 million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.Comment: To appear in Nature on May 10, 201

Preoperative computed tomography staging of nonmetastatic colon cancer predicts outcome: implications for clinical trials

Colon cancer patients routinely undergo preoperative computed tomography (CT) scanning, but local staging is thought to be inaccurate. We aimed to determine if clinical outcome could be predicted from radiological features of the primary tumour. Consecutive patients at one hospital undergoing primary resection for colon cancer during 2000–2004 were included. Patients with visible metastases were excluded. Preoperative CT scans were reviewed independently by two radiologists blinded to histological stage and outcome. Images of the primary tumour were evaluated according to conventional TNM criteria and patients were stratified into ‘good' or ‘poor' prognosis groups. Comparison was made between prognostic group and actual clinical outcome. Hundred and twenty-six preoperative CT scans were reviewed. T-stage and nodal status was correctly predicted in only 60 and 62%, respectively. However, inter-observer agreement for prognostic group was 79% (κ=0.59) and 3-year relapse-free survival was 71 and 43% for the CT-predicted ‘good' and ‘poor' groups, respectively (P<0.0066). This compared favourably with 75 vs 43% for histology-predicted prognostic groups. Computed tomography is a robust method for stratifying patients preoperatively, with similar accuracy to histopathology for predicting outcome. Recognition of poor prognosis tumours preoperatively may permit investigation into the future use of neo-adjuvant therapy in colon cancer

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases

Development of a perioperative medicine research agenda: a cross sectional survey

BACKGROUND: Post-operative complications are a significant source of morbidity and mortality for patients undergoing surgery. However, there is little research in the emerging field of perioperative medicine beyond cardiac risk stratification. We sought to determine the research priorities for perioperative medicine using a cross sectional survey of Canadian and American general internists. METHODS: Surveys were electronically sent to 312 general internists from the Canadian Society of Internal Medicine and 130 internists from the perioperative medicine research interest group within the US based Society of General Internal Medicine. The questionnaire contained thirty research questions and respondents were asked to rate the priority of these questions for future study. RESULTS: The research topics with the highest ratings included: the need for tight control of diabetes mellitus postoperatively and the value of starting aspirin on patients at increased risk for postoperative cardiac events. Research questions evaluating the efficacy and safety of perioperative interventions had higher ratings than questions relating to the prediction of postoperative risk. Questions relating to the yield of preoperative diagnostic tests had the lowest ratings (p < 0.001 for differences across these categories). CONCLUSION: The results of this survey suggest that practicing general internists believe that interventions studies are a priority within perioperative medicine. These findings should help prioritize research in this emerging field